Protein mutation support in Neq Cycling Setup Unit #106

ijpulidos · 2025-01-30T17:34:06Z

These changes aim to add support to be able to perform protein mutations in the current SetupUnit that the NonEquilibriumCyclingProtocol uses.

This mostly implies making sure that the alchemical component is now not assumed to be a SmallMoleculeComponent but also a ProteinComponent.

Utility functions for achieving such purpose were written or modified accordingly. Someof these changes were needed to be made on the openfe side of things, since we have not yet decided on migrating them to feflow (this code base).

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…ols comps

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IAlibay

Couple of things but otherwise lgtm.

IAlibay · 2025-12-16T00:16:18Z

devtools/conda-envs/test_env.yaml

+  - gufe ~=1.7.1
  - numpy
-  - openfe >=0.15  # TODO: Remove once we don't depend on openfe
+  - openfe ~=1.7.0   # TODO: Remove once we don't depend on openfe


We're at 1.8 now, but that might be better bumped in a separate PR.

I think I need to change it here since I'm also bumping the python version. Hopefully it would "just work". THanks for the heads up.

IAlibay · 2025-12-16T00:17:01Z

docs/tutorials/protein-mutations-neq.ipynb

@@ -0,0 +1,49 @@
+{


Love the idea of a tutorial, but I would recommend just bumping it to a separate PR.

I already worked on a tutorial, lives in https://github.com/OpenFreeEnergy/feflow/blob/protein-mutation-setup/docs/tutorials/protein-mutations-neq.ipynb

I guess we could consider moving it to the OpenFE Example Notebooks instead in the future.

IAlibay · 2025-12-16T00:19:55Z

feflow/protocols/protein_mutation.py


-class ProteinMutationProtocol(Protocol):
-    pass
+ProteinMutationProtocol = NonEquilibriumCyclingProtocol


Still todo to remove?

IAlibay · 2025-12-16T00:49:51Z

feflow/utils/misc.py

+    return topology
+
+
+def get_positions_from_component(


We can limit it to ExplicitComponents, that way SolventComps don't have it.

IAlibay · 2025-12-16T00:51:03Z

feflow/utils/misc.py

+    ValueError
+        If the atom index is not found in the topology.
+    """
+    for residue in topology.residues():


Definitely would remove if it's not doing anything.

IAlibay · 2025-12-16T00:53:22Z

feflow/protocols/nonequilibrium_cycling.py

+        solvent_comp_a = (
+            solvent_comps.pop() if solvent_comps else None
+        )  # there must be at most one solvent comp


If you're already volidating it to be a single component, do you need to go thought this? I.e. could you not just make solvents_comp_a == solvent_comps?

Yes. That's true, I will validate in the _validate method of the protocol, and improve the logic here. The only caveat is that some utility functions expect the component itself, some other expect a list of components (because they are meant to be used for non-solvent components as well), but that shouldn't be an issue. Maybe something we want to change in the future, for all "utils" to have the same typing signature?

IAlibay · 2025-12-16T01:23:55Z

feflow/protocols/nonequilibrium_cycling.py

            integrator_settings=integrator_settings,
            cache=ffcache,
-            has_solvent=solvent_comp is not None,
+            has_solvent=bool(solvent_comp_a),


[nit] As far as I know, PEP8 does prefer var is not None over bool(var)

IAlibay · 2025-12-16T01:27:54Z

feflow/protocols/nonequilibrium_cycling.py

        elif alchemical_settings.softcore_LJ.lower() == "beutler":
            softcore_LJ_v2 = False
+        # TODO: We need to test HTF for protein mutation cases, probably.
+        #  What are ways to quickly check an HTF is correct?


Do you mean in terms of testing the hyrid system? Easiest way is to check if the endstates match the energy of the non-alchemical systems.

That's a good suggestion, I think I'll bump that to a future PR, but sounds like something we could do. Issue raised in #134

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ijpulidos and others added 8 commits November 20, 2024 11:32

ADding TODO/Comments for things to refactor/review.

fb4b088

Removing unneeded todo

a6a1705

Fix custom exceptions in tests

24ccc77

Refined dependencies

086f246

Misc utility functions and tests

e997aea

Adding miscellaneous utility functions

8fd3877

Using new utility funcs from both feflow and openfe (branch)

ad4ef62

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ijpulidos marked this pull request as draft January 30, 2025 18:03

ijpulidos linked an issue Jan 30, 2025 that may be closed by this pull request

Refactor setup unit to work with protein mutation protocol #77

Closed

ijpulidos added 5 commits January 30, 2025 13:34

Using protein mutation support openfe branch for now

08aedfe

remove conda-forge openfe dependency for now

9ad227a

Adding temporary dependencies

5134755

WIP -- fixing tests and TODOs

c35439e

Doesn't make sense to detect phase. Better name for unit.

1139eb2

jameseastwood assigned ijpulidos Mar 5, 2025

ijpulidos and others added 14 commits March 25, 2025 17:16

Add utility function to get residue indices in chain

9b2e508

Using mapped atoms instead of unique, since unique can be empty.

5784daa

Using updated arg name

1669449

Test gly to ala. Useful for removing atoms instead of adding.

e32bb67

[pre-commit.ci] auto fixes from pre-commit.com hooks

aa3ffc2

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Adding threadpoolctl missing dep

f10415e

Using gufe from git. Temporarily.

9a8b99c

Adding needed dependency for gufe

a1106b2

Pinning lower lomap version

34b3a4d

directly getting solvent component

e360385

[pre-commit.ci] auto fixes from pre-commit.com hooks

330a3c3

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Handle topologies with multiple chains by checking all atoms

cbd49f3

[pre-commit.ci] auto fixes from pre-commit.com hooks

afa6b95

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Adding way to store minmized topology pdb. Minor fixes comments/docs.

994c2ca

ijpulidos and others added 6 commits November 17, 2025 14:54

sorting parameters for unambiguity with pytest-xdist

fbfa750

Removing unnecessary utility function

1ce2be0

Warning about partial charges difference between template and small m…

5d2d062

…ols comps

Checking instances types instead. Helpful error msg.

a55e2f4

[pre-commit.ci] auto fixes from pre-commit.com hooks

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Removing protein mutation module. No need.

19149b4

IAlibay approved these changes Dec 16, 2025

View reviewed changes

ijpulidos and others added 7 commits December 16, 2025 19:51

More comprehensive testing. Unskipping test.

766fc6c

Adding first iteration of tutorial

c2a262c

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7019101

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Updating python version for CI. Dropping 3.10

156b0c2

Removing erroneous import

03f8c20

Improved logic, expecting just one solvent.

1df3a91

Removing unused utility function.

d713d84

ijpulidos mentioned this pull request Dec 18, 2025

Testing HTF end states for protein mutation #134

Open

ijpulidos and others added 9 commits December 18, 2025 11:53

Avoiding xdist test limitation in MacOS

332489f

Requiring latest openfe 1.8

3da59a9

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Fixing typo in minor release

abd8dc9

Allowing for no solvent as well.

1a7ab08

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9bb9630

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Not supporting 3.13 for the moment due to espaloma limitations

1b1c3f5

Using correct protocol. And express/short settings.

3536bfc

Adding image for protein mutation tutorial

596bd2e

ijpulidos changed the title ~~[DNM] Protein mutation support in Neq Cycling Setup Unit~~ Protein mutation support in Neq Cycling Setup Unit Dec 19, 2025

ijpulidos merged commit 570ec7c into protein-mutation-protocol Dec 19, 2025
6 checks passed

ijpulidos deleted the protein-mutation-setup branch December 19, 2025 03:37

This was referenced Dec 19, 2025

Protein mutation protocol #132

Merged

Update SetupUnit phase detection #72

Closed

Create a ProteinMapping subclass #74

Open

Protein mutation support in Neq Cycling Setup Unit #106

Protein mutation support in Neq Cycling Setup Unit #106

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ijpulidos commented Jan 30, 2025

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